Picture of Priya Gatti

The epilepsy-associated RabGAP protein TBC1D24 is one of the proteins mutated in DOORS syndrome (Deafness, Onycho-Osteodystrophy, mental Retardation, Seizures). At the molecular level, TBC1D24 has been shown to interact with vesicular transport regulators and to be important for the recycling of synaptic vesicles. Intriguingly, some patients with TBC1D24-related epilepsy also show signs of mitochondrial disease (e.g., increased plasma lactate, decreased mitochondrial respiratory chain complex activities on live or muscle biopsies), suggesting a potential role of TBC1D24 in mitochondrial function. This possibility will be explored by TBC1D24 expert Campeau and mitochondrial expert Germain, with the idea to better understand and eventually treat the mitochondrial disease associated with TBC1D24 deficiency. They will do this by first determining whether TBC1D24 associates with mitochondria and certain mitochondrial proteins using proteomics (with the help of the Mass Spectrometry core) and biochemical approaches in human cells. They will also assess the effect of TBC1D24 deficiency on mitochondria morphology (fusion, fission, shape and network) and function (mitochondrial membrane potential, respiratory chain complex activity and integrity, oxygen consumption rate). This will be important to understand the consequences of TBC1D24 deficiency, and eventually test new therapies.

Principal investigator: Pr Philippe Campeau (CHU Sainte-Justine)
Collaborator: Marc Germain
Laureate: 2019 Collaborative Research Grant